Coupled Genome-Wide DNA Methylation and Transcription Analysis Identified Rich Biomarkers and Drug Targets in Triple-Negative Breast Cancer.

摘要: Triple-negative breast cancer (TNBC) has poor clinical prognosis. Lack of TNBC-specific biomarkers prevents active intervention. We reasoned that TNBC must have its specific signature due to the lack three key receptors distinguish from other types cancer. also coupling methylation and gene expression as a single unit may increase specificity for detected signatures. further choosing proper controls be critical increasing sensitivity identify Furthermore, we considered drugs could target developed system potential It consisted (1) changes in methylation-regulated genes TNBC; (2) using TPBC (triple-positive cancer) control detect genes; (3) searching drug database those targeting genes. Using this system, identified 114 with both altered expression, 356 existing 10 Through docking molecular dynamics simulation, determined structural basis between sapropterin, used treatment tetrahydrobiopterin deficiency, PTGS2, involved conversion arachidonic acid prostaglandins. Our study reveals existence rich signatures, many can biomarker candidates applications.